Vaccine Therapy in Treating Patients With Stage IV Melanoma

Sponsor

Mannkind Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT00033228

Collaborator

(none)

Enrollment

Locations

Arms

14.9

Duration (Months)

3.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Infusing the vaccine directly into a lymph node may cause a stronger immune response and kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage IV melanoma.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Biological: MKC1106-MT Biological: MKC1106-MT Biological: MKC1106-MT	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of intranodal Synchrovax SEM plasmid DNA vaccine in patients with stage IV melanoma.
Determine the safety and tolerability of this drug in these patients.
Determine the immunological response, as measured by changes in frequency of T cells specific against vaccine-encoded epitopes before and after treatment, in patients treated with this drug.
Determine the clinical response, as measured by lactic dehydrogenase levels and radiologic assessment of lesions, in patients treated with this drug.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive Synchrovax SEM plasmid DNA vaccine by continuous intranodal infusion on days 1-4. Treatment repeats every 14 days for up to 4 courses in the absence of unacceptable toxicity. Patients with evidence of stable or responding disease are eligible for 4 additional courses of treatment.

Cohorts of 6 patients receive escalating doses of Synchrovax SEM plasmid DNA vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 10 days after the last dose of study drug.

PROJECTED ACCRUAL: A total of 6-18 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II Pilot Study Of Intranodal Delivery Of A Plasmid DNA (Synchrovax SEM Vaccine) In Stage IV Melanoma Patients

Study Start Date :

Jan 1, 2002

Actual Primary Completion Date :

Mar 1, 2003

Actual Study Completion Date :

Apr 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 The first cohort of 6 patients received 500 ug of Synchrovax SEM plasmid DNA vaccine. All patients were to be monitored for dose limiting toxicities DLTs) for a minimum of 2 weeks after their second infusion of vaccine on Day 15 before allowing patients to enroll at the next dose group. The decision to progress to the next dose group was to be based on occurrence of DLTs observed in 1 or fewer (<33%) patients of a 6 patient cohort.	Biological: MKC1106-MT Cancer Vaccine, Immunotherapy, 500 ug
Experimental: Cohort 2 The second cohort of 6 patients received 1000 ug of Synchrovax SEM plasmid DNA vaccine. All patients were to be monitored for dose limiting toxicities DLTs) for a minimum of 2 weeks after their second infusion of vaccine on Day 15 before allowing patients to enroll at the next dose group. The decision to progress to the next dose group was to be based on occurrence of DLTs observed in 1 or fewer (<33%) patients of a 6 patient cohort.	Biological: MKC1106-MT Cancer Vaccine, Immunotherapy, 1000 ug
Experimental: Cohort 3 The third cohort of 6 patients received 1500 ug of Synchrovax SEM plasmid DNA vaccine. The maximum tolerated dose (MTD) was to be determined by the observation of DLT at each dose group.	Biological: MKC1106-MT Cancer Vaccine, Immunotherapy, 1500 ug

Arm

Intervention/Treatment

Experimental: Cohort 1

The first cohort of 6 patients received 500 ug of Synchrovax SEM plasmid DNA vaccine. All patients were to be monitored for dose limiting toxicities DLTs) for a minimum of 2 weeks after their second infusion of vaccine on Day 15 before allowing patients to enroll at the next dose group. The decision to progress to the next dose group was to be based on occurrence of DLTs observed in 1 or fewer (<33%) patients of a 6 patient cohort.

Biological: MKC1106-MT

Cancer Vaccine, Immunotherapy, 500 ug

Experimental: Cohort 2

The second cohort of 6 patients received 1000 ug of Synchrovax SEM plasmid DNA vaccine. All patients were to be monitored for dose limiting toxicities DLTs) for a minimum of 2 weeks after their second infusion of vaccine on Day 15 before allowing patients to enroll at the next dose group. The decision to progress to the next dose group was to be based on occurrence of DLTs observed in 1 or fewer (<33%) patients of a 6 patient cohort.

Biological: MKC1106-MT

Cancer Vaccine, Immunotherapy, 1000 ug

Experimental: Cohort 3

The third cohort of 6 patients received 1500 ug of Synchrovax SEM plasmid DNA vaccine. The maximum tolerated dose (MTD) was to be determined by the observation of DLT at each dose group.

Biological: MKC1106-MT

Cancer Vaccine, Immunotherapy, 1500 ug

Outcome Measures

Primary Outcome Measures

The primary objective of the study was to evaluate the safety and tolerability of Synchrovax® pSEM Vaccine measured by the adverse event and severe adverse event profile. []

Secondary Outcome Measures

The secondary objective of the study was to determine the immunological response of patients as measured by tetramer assay and to assess clinical response by LDH levels and radiological assessment of lesions. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed stage IV melanoma
Must have tumor tissue available for determining antigen expression
At least 10% of tumor cells must stain positive for Melan-A/Mart-1 by immunohistochemistry
HLA-A2 positive
No brain metastases unless completely resected or without evidence of disease after treatment

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-1

Life expectancy:

More than 3 months

Hematopoietic:

Absolute neutrophil count at least 1,500/mm3
WBC at least 3,000/mm3
Platelet count at least 75,000/mm3
Hemoglobin at least 9 g/dL

Hepatic:

SGOT and SGPT no greater than 2.5 times upper limit of normal (ULN)
Alkaline phosphatase no greater than 2.5 times ULN
Bilirubin no greater than 1.5 times ULN
Hepatitis B surface antigen negative
Hepatitis C antibody negative

Renal:

Creatinine no greater than 1.5 times ULN
Urea no greater than 2.6 times ULN

Other:

Not pregnant, nursing, or planning to become pregnant within 6 months of treatment completion
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
No medical, sociological, or psychological impediments that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 4 weeks since prior immunotherapy
At least 4 weeks since prior immunomodulatory drugs
No other concurrent immunotherapy
No concurrent immunomodulatory drugs

Chemotherapy:

At least 4 weeks since prior chemotherapy
No concurrent chemotherapy

Endocrine therapy:

At least 4 weeks since prior systemic corticosteroids
No concurrent systemic corticosteroids

Radiotherapy:

At least 4 weeks since prior radiotherapy
No concurrent radiotherapy

Surgery:

See Disease Characteristics

Other:

At least 4 weeks since prior investigational drugs
No other concurrent investigational drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724
2	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089
3	Cancer Research Center at Boston Medical Center	Boston	Massachusetts	United States	02118
4	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
5	Earle A. Chiles Research Institute at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967

Sponsors and Collaborators

Mannkind Corporation

Investigators

Study Chair: Chief Scientific Officer, Mannkind Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00033228

Other Study ID Numbers:

CDR0000069252
CTL-26-35

First Posted:

Jan 27, 2003

Last Update Posted:

May 12, 2011

Last Verified:

May 1, 2011

Keywords provided by , ,

stage IV melanoma

recurrent melanoma

Additional relevant MeSH terms:

Melanoma

Study Results

No Results Posted as of May 12, 2011